Sun Yue, Jin Shi-Dai, Zhu Quan, Han Liang, Feng Jing, Lu Xi-Yi, Wang Wei, Wang Feng, Guo Ren-Hua
Department of Oncology, Yancheng Third People's Hospital, The Affiliated Yanchen Hospital of Southeast University Medicine College, Yancheng, Jiangsu, China.
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Oncotarget. 2017 Apr 25;8(17):28297-28311. doi: 10.18632/oncotarget.16044.
Recently, long non-coding RNAs (lncRNAs) have been recognized as playing key roles in regulating cellular processes, such as proliferation, invasion, and metastasis. These lncRNAs have been shown to be abnormally expressed in tumorigenic processes. However, the role and clinical relevance of LUCAT1 in non-small-cell lung cancer (NSCLC) remain unclear. In this study, we found that the expression of LUCAT1 was significantly up-regulated in NSCLC tissues compared to non-tumor tissues, and its expression was associated with tumor size, tumor-node-metastasis (TNM) stage and overall survival (OS). Further experiments showed that LUCAT1 knockdown inhibited cell proliferation both in vitro and in vivo. Mechanistic investigations showed that LUCAT1 plays a key role in G0/G1 arrest. We further demonstrated that LUCAT1 was associated with polycomb repressor complexes (PRC2) and that this association was required for epigenetically repression of p21 and p57, thus contributing to the regulation of NSCLC cell cycle and proliferation. In summary, our results show that LUCAT1 could regulate tumorigenesis of NSCLC and be biomarker for poor prognosis in NSCLC.
最近,长链非编码RNA(lncRNAs)已被认为在调节细胞过程中发挥关键作用,如增殖、侵袭和转移。这些lncRNAs已被证明在肿瘤发生过程中异常表达。然而,LUCAT1在非小细胞肺癌(NSCLC)中的作用和临床相关性仍不清楚。在本研究中,我们发现与非肿瘤组织相比,LUCAT1在NSCLC组织中的表达显著上调,并且其表达与肿瘤大小、肿瘤-淋巴结-转移(TNM)分期和总生存期(OS)相关。进一步的实验表明,敲低LUCAT1在体外和体内均抑制细胞增殖。机制研究表明,LUCAT1在G0/G1期阻滞中起关键作用。我们进一步证明LUCAT1与多梳抑制复合物(PRC2)相关,并且这种关联是p21和p57表观遗传抑制所必需的,从而有助于调节NSCLC细胞周期和增殖。总之,我们的结果表明,LUCAT1可调节NSCLC的肿瘤发生,并可作为NSCLC预后不良的生物标志物。